New Zealand Black (NZB) and NZB/NZW F1 mice spontaneously develop lymphoma and monoclonal macroglobulinemia as they age. These problems arise in animals surviving their autoimmune disease which develops earlier in life. Malignant lymphoma and monoclonal macroglobulinemia also develop in patients with autoimmune diseases. This proposal will study the relationship between lymphoma, macroglobulinemia and autoimmunity. A transplantable lymphoma (141) producing monoclonal IgM will be studied for antibody activity of the IgM and surface idiotypes that can function as tumor specific transplantation antigens. We will attempt to induce specific cytotoxicity against the lymphoma by immunization against idiotype determinants present on the monoclonal immunoglobulin. Similar experiments will be performed with CAF1 plasma cell tumor producing a myeloma globulin that binds DNA. We will attempt to prevent anti-DNA formation in immunized CAF1 mice and in diseased NZB/NZW mice by specific immunotherapy directed against the idiotype of this anti-DNA myeloma.